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Artículo

AKT/GSK3β signaling pathway is critically involved in human pluripotent stem cell survival

Romorini, LeonardoIcon ; Garate, XimenaIcon ; Neiman, GabrielIcon ; Luzzani, Carlos DanielIcon ; Furmento, Verónica AlejandraIcon ; Guberman, Alejandra SoniaIcon ; Sevlever, Gustavo; Scassa, Maria Elida; Miriuka, Santiago GabrielIcon
Fecha de publicación: 10/2016
Editorial: Nature Publishing Group
Revista: Scientific Reports
ISSN: 2045-2322
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Ciencias Biológicas

Resumen

Human embryonic and induced pluripotent stem cells are self-renewing pluripotent stem cells (PSC) that can differentiate into a wide range of specialized cells. Basic fibroblast growth factor is essential for PSC survival, stemness and self-renewal. PI3K/AKT pathway regulates cell viability and apoptosis in many cell types. Although it has been demonstrated that PI3K/AKT activation by bFGF is relevant for PSC stemness maintenance its role on PSC survival remains elusive. In this study we explored the molecular mechanisms involved in the regulation of PSC survival by AKT. We found that inhibition of AKT with three non-structurally related inhibitors (GSK690693, AKT inhibitor VIII and AKT inhibitor IV) decreased cell viability and induced apoptosis. We observed a rapid increase in phosphatidylserine translocation and in the extent of DNA fragmentation after inhibitors addition. Moreover, abrogation of AKT activity led to Caspase-9, Caspase-3, and PARP cleavage. Importantly, we demonstrated by pharmacological inhibition and siRNA knockdown that GSK3β signaling is responsible, at least in part, of the apoptosis triggered by AKT inhibition. Moreover, GSK3β inhibition decreases basal apoptosis rate and promotes PSC proliferation. In conclusion, we demonstrated that AKT activation prevents apoptosis, partly through inhibition of GSK3β, and thus results relevant for PSC survival.
Palabras clave: Akt Signalling , Pluripotent Cells , Cell Survival
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/56344
DOI: https://dx.doi.org/10.1038/srep35660
URL: https://www.nature.com/articles/srep35660
Colecciones
Articulos(IQUIBICEN)
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Citación
Romorini, Leonardo; Garate, Ximena; Neiman, Gabriel; Luzzani, Carlos Daniel; Furmento, Verónica Alejandra; et al.; AKT/GSK3β signaling pathway is critically involved in human pluripotent stem cell survival; Nature Publishing Group; Scientific Reports; 6; 3566; 10-2016; 1-15
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